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Biomedical subjects

I Grant

Publications and source records attributed to I Grant.

At least 19 recordsLinked to original sources

Is gender dysphoria dysphoric? Elevated depression and anxiety in gender dysphoric and nondysphoric homosexual and bisexual men in an HIV sample. HNRC Group.

Few if any studies before the AIDS epidemic suggested that male homosexuals may on average have higher levels of depression than male heterosexuals. However, several samples of homosexual and bisexual men in HIV studies suggest that depression and anxiety are high in these populations, and that this psychiatric morbidity began before the AIDS epidemic. We tested the hypothesis that high childhood gender nonconformity (CGN) is associated with depression and anxiety, and so might account for differences in these variables among samples of homosexuals. A total of 254 homosexual or bisexual male subjects were assessed for depression, anxiety, and associated symptoms using various self-report and interview measures, as well as for CGN (using the Freund Feminine Gender Identity scale, FGI). For comparison purposes only, we also evaluated the subjects for the DSM-III diagnosis of Ego-Dystonic Homosexuality. Highly gender nonconforming men (high FGI scores) were more likely to have current symptoms of anxiety and depression by self-report, and to have had a lifetime history of depression by clinical interview. This association was more often due to FGI items dealing with childhood than adulthood. When the FGI was broken into subscales by a prior factor analysis, stepwise regression suggested that the subscale measuring core gender identity nonconformity (so-called "gender dysphoria") was more reliably associated with depression and anxiety than were the factors measuring nonconformity in the areas of masculine and feminine gender roles, or genitoerotic (sexual) roles. This subscale was also the only FGI measure correlating with Ego-Dystonic Homosexuality. AIDS (CDC stage and HIV serostatus) and age did not account for these findings. We conclude that the often-reported higher levels of depression, anxiety, and associated symptoms among homosexual and bisexual men in AIDS studies are more common in the subgroup of such men who are gender dysphoric. Theoretical and clinical implications of these data are discussed.

Adult

Stress, vulnerability and adult alcohol relapse.

OBJECTIVE: Alcoholics experiencing highly threatening or chronic psychosocial stress following treatment are more likely to relapse than abstaining individuals not experiencing such stress. Expanding upon this stress-relapse hypothesis, we predicted that individual risk and protective characteristics would contribute to vulnerability to relapse in alcoholic men confronted with significant life adversity. The present investigation examined the relationship between psychosocial vulnerability and return to drinking. METHOD: A group of abstinent male alcoholics (N = 67) who experienced marked life adversity that posed a severe and/or chronic threat participated in this study. Men completed a psychosocial assessment first as an inpatient in treatment for alcohol dependence, and again at 3 months and 1 year following discharge. RESULTS: Among alcoholic men exposed to severe psychosocial stressors, those with higher composite psychosocial vulnerability scores were more likely to subsequently relapse than those with lower vulnerability scores. Additionally, men who improved in psychosocial functioning following treatment had better outcomes than men whose vulnerability increased. In particular, coping, self-efficacy and social support most consistently predicted relapse among this sample of severely stressed abstaining alcoholics. CONCLUSIONS: These findings supported the stress-vulnerability model of relapse. Results indicated that improvement in psychosocial domains (e.g., coping skills, social networks, perceived ability to tolerate relapse-risk situations) enhanced the ability of these men to remain abstinent despite severe stress. This study highlights the importance of cognitive and behavioral interventions for increasing improvement in these psychosocial domains.

Adaptation, Psychological

Neurological dysfunction in asymptomatic HIV-1 infected men: evidence from evoked potentials. HNRC Group.

Neurological function in 159 subjects infected by the human immunodeficiency virus (HIV) who had no neurological symptoms or signs (129 asymptomatic, 30 with ARC/AIDS) was compared to that of 62 controls by means of pattern-reversal evoked potentials (PREPs), brain-stem auditory evoked potentials (BAEPs), median nerve somatosensory evoked potentials (MSEPs), tibial nerve somatosensory evoked potentials (TSEPs) and nerve conduction studies (NCSs). Central nervous system somatosensory conduction from lumbar cord to cortex was prolonged in both asymptomatic seropositive and ARC/AIDS groups, while peripheral somatosensory conduction, NCSs and PREP delays occurred only in the ARC/AIDS group. BAEPs did not show significant differences among groups. TSEPs were abnormal in 8% of asymptomatic carriers and 43% of patients with ARC/AIDS, MSEPs in 7% and 20%, PREPs in 4% and 0%, and BAEPs in 1% and 0% respectively. One or more evoked potentials were abnormal in 18 of 129 (14%) asymptomatic carriers and 13 of 30 (43%) subjects with ARC/AIDS as compared with 1 of 62 (2%) seronegative controls. We conclude that asymptomatic HIV carriers have subclinical neurological impairment of central somatosensory function and that the neurological impairment increases with disease progression to involve peripheral nerves and visual system.

Adolescent

Responses of tissue protein synthesis to nutrient intake in rats exposed to interleukin-1 beta or turpentine.

1. The influence of an acute-phase reaction on the ability of protein synthesis rates in liver and three different muscles (gastrocnemius, soleus and heart) to respond to a short intravenous infusion of nutrients (glucose plus amino acids) was investigated during experimental inflammation induced by injection of human recombinant interleukin-1 beta or turpentine in young male rats. 2. Interleukin-1 beta induced a consistent increase of 3 degrees C in body temperature between 3 and 5 h after injection, whereas turpentine induced a delayed fever, peaking by 13 h. 3. Interleukin-1 beta and turpentine stimulated fractional rates of protein synthesis in liver. The synthesis rate was inhibited by interleukin-1 beta in gastrocnemius and soleus muscle, but an elevation was seen in heart muscle. In this study there was no significant response of muscle to turpentine injection. 4. Two hours of parenteral nutrition increased fractional synthesis rates in all tissues when compared with Ringer's lactate. Somewhat larger responses to feeding were observed as a result of either interleukin-1 beta or turpentine injection in all tissues, but these improvements were not significant. 5. We conclude that the response of protein synthesis rates in liver and skeletal muscle to parenteral nutrition is not inhibited, and may be somewhat enhanced, during acute inflammatory conditions in the growing rat.

Acute-Phase Proteins

Reduced mortality risk in alcoholics who achieve long-term abstinence.

OBJECTIVES: To determine if alcoholic men who achieved stable abstinence experienced fewer deaths than those who relapsed and to develop a model predictive of premature mortality. DESIGN: A cohort of alcoholic men recruited into a prospective study of neurocognitive effects of alcoholism was followed up from 1 through 11 years. A demographically equated group of nonalcoholic men was also followed up. Alcoholics were classified as stable abstainers or relapsers. SETTING: Alcoholics were patients or ex-patients from a Department of Veterans Affairs Alcoholism Treatment Program and/or members of local chapters of Alcoholics Anonymous. PARTICIPANTS: There were 234 alcoholic men who met the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, criteria for alcohol dependence. Follow-up status regarding relapse and mortality was obtained for 199 alcoholic subjects (85%). Of these, 101 had relapsed and 98 had abstained. Ninety-eight nonalcoholic controls equated for age, education, and sex also participated. Mortality status was obtained for 92 subjects in this group (94%). EXCLUSIONS: Major medical and psychiatric illness and history of nonalcoholic drug abuse. MAIN OUTCOME MEASURE: Death during a follow-up period of 1 through 11 years. Death was ascertained through the National Death Index, the California State Department of Health and Vital Statistics, the State Department of Motor Vehicles, and through personal contact with informants, relatives, and significant others of the subjects. RESULTS: There were 19 deaths among relapsed alcoholics compared with the expected number of 3.83 (99% confidence interval (CI), 9.64 to 33.38). Among abstinent alcoholics there were four deaths (expected = 3.21; 99% CI, 0.67 to 12.59). The standardized mortality ratio for relapsed alcoholics was 4.96, which significantly exceeded the expected ratio (P less than .001), whereas the standardized mortality ratio for abstinent alcoholics (1.25) was indistinguishable from the expected. Cox proportional hazards analysis was used to determine if any of several demographic, medical, cognitive, or drinking history variables (in addition to relapse) helped predict mortality among alcoholics. Only relapse was significantly related to increased mortality (chi 2 = 9.15, P = .003). CONCLUSIONS: Alcoholic men who achieve stable abstinence do not differ from nonalcoholic men in mortality experience; however, alcoholics who relapse die at a rate 4.96 times that of an age-, sex-, and race-matched representative sample from the US Bureau of the Census.

Alcoholism

Visual dysfunction without retinitis in patients with acquired immunodeficiency syndrome.

Patients with human immunodeficiency virus infection may have noninfectious and infectious retinopathies, as well as clinical symptoms consistent with optic nerve dysfunction. Noninfectious acquired immunodeficiency syndrome-related retinopathy is seen in most patients with AIDS. Morphologic studies have shown that the number of retrobulbar optic nerve fibers in patients with AIDS is decreased compared to the number of optic nerve fibers in normal control eyes. To determine whether these patients had a visual dysfunction consistent with damage to the macula and optic nerve, 78 subjects (156 eyes) were studied using color-vision and contrast-sensitivity testing. The Farnsworth-Munsell 100-Hue color-vision test was performed on all subjects and age-corrected color-vision scores for all groups were compared. A significant decrease in color discrimination was found in the patients with AIDS (P less than .001). Contrast-sensitivity testing disclosed a deficit of contrast threshold in patients with AIDS at four of five spatial frequencies and in patients with AIDS-related complex at three of the five spatial frequencies examined. This study demonstrated a functional visual deficit in eyes without retinitis consistent with dysfunction of the macula or optic nerve in patients with AIDS.

Acquired Immunodeficiency Syndrome

Sensory testing in human immunodeficiency virus type 1-infected men. HIV Neurobehavioral Research Center Group.

Patients with acquired immunodeficiency syndrome frequently suffer peripheral neuropathy. We investigated its prevalence and relationship to clinical stage of human immunodeficiency virus (HIV) infection using quantitative sensory testing and nerve conduction testing. Vibratory threshold was determined in the right great toe and index finger of 179 men seropositive for HIV (28 with acquired immunodeficiency syndrome [AIDS] or AIDS-related complex [ARC], 151 asymptomatic) and 32 HIV-seronegative controls. None had clinical peripheral neuropathy. Abnormal threshold was control mean plus 2.5 SDs. In the toe, 10 (36%) of 28 subjects with AIDS or ARC had abnormal vibratory thresholds, compared with seven (5%) of 151 asymptomatic seropositive subjects and none of 32 controls. A subgroup of 168 seropositive subjects underwent nerve conduction testing. Abnormality rates were similar, but abnormalities of nerve conduction coincided with quantitative sensory testing abnormalities in only half the cases. Mean (+/-SD) vibratory threshold was significantly greater in subjects with AIDS or ARC (3.00 +/- 0.51 vibratory units) than in asymptomatic subjects (1.56 +/- 0.27 vibratory units) and controls (1.63 +/- 0.54 vibratory units). Finger abnormality rates did not differ, although subjects with AIDS or ARC had greater mean vibratory threshold. Subclinical peripheral neuropathy is thus related to stage of HIV infection and is present by quantitative sensory testing in 36% of patients with AIDS or ARC.

AIDS-Related Complex

The determination of low d5-phenylalanine enrichment (0.002-0.09 atom percent excess), after conversion to phenylethylamine, in relation to protein turnover studies by gas chromatography/electron ionization mass spectrometry.

A gas chromatography/mass spectrometry (GC/MS) method for measuring very low levels of enrichment of d5-phenylalanine (0.002-0.09 atom percent excess) is described. This method makes it possible to determine the enrichment of amino acid incorporated into tissue protein during studies of protein synthesis in man. Phenylalanine is enzymatically converted to phenylethylamine and the d5-enrichment is measured in the heptafluorobutyryl derivative by selective-ion recording under electron ionization conditions. The coefficients of variation for muscle-protein hydrolysate samples enriched with d5-phenylalanine at the 0.005 and 0.05 atom percent excess levels were 6.0 and 1.2%, respectively. This precision at low enrichment and the small amount of protein needed (about 1 mg) provide real advantages for clinical studies of tissue protein synthesis. Moreover, in contrast to the conventional approach which uses GC/MS for plasma amino acids (typically 2-20 atom percent excess) but gas isotope-ratio mass spectrometry for protein-bound amino acids, the enrichment of both plasma-free and protein-bound d5-phenylalanine can be measured with a single instrument.

Gas Chromatography-Mass Spectrometry

Symptoms of illness in late adulthood are related to childhood social deprivation and misfortune in men but not in women.

Experiencing adverse life events during childhood may increase vulnerability to physical illnesses and psychological disorders during adulthood. We developed an Early Life Events Questionnaire (ELEQ) with 12 scales and administered it to 92 relatively healthy elderly individuals (29 men and 63 women). A canonical-correlation analysis of the 12 ELEQ scales and physical and psychological symptoms revealed a significant canonical correlation. The results indicate that those who grew up in a family with a harsh climate and whose affiliation needs were not met tended to have more psychological and physical symptoms in old age. Regression analysis revealed that, in men, early life events accounted for 42% of the variance in physical symptoms and 39% in psychological symptoms. No significant relationship, however, was found between ELEQ scales and health outcomes in women. These results suggest that women may be less vulnerable than men to the adverse health consequences of childhood deprivation and other misfortunes.

Age Factors

Effects of recalled childhood gender nonconformity on adult genitoerotic role and AIDS exposure. HNRC Group.

The connections between childhood gender nonconformity (assessed by the Freund Feminine Gender Identity Scale, or FGI) and adult genitoerotic role (assessed by a sex history) were examined. The core sample was a group of 106 men who had sex with other men before 1980 and who are currently enrolled in two longitudinal studies of AIDS. Although other workers have cautioned against assuming a priori that childhood gender role is inherently related to adult preferences for particular sexual acts, our data suggest that there is at least a statistical association between these two concepts. In particular, the FGI (and many of its factors and items) are significantly associated with preferences for receptive anal intercourse and, less clearly, with oral-anal contact--but not with oral-genital intercourse or insertive and intercourse. Suggestions for AIDS prevention and safe-sex awareness are made on the basis of these findings. The data also suggest that in sex research involving homosexual men, the correct genitoerotic role distinction is not insertive vs. receptive behaviors, or even insertive vs. receptive and intercourse, but receptive anal intercourse vs. all other behaviors.

Acquired Immunodeficiency Syndrome

Epidural blood patch in the HIV-positive patient. Review of clinical experience. San Diego HIV Neurobehavioral Research Center.

To characterize the natural history of autologous epidural blood patch (EBP) in human immunodeficiency virus (HIV)-seropositive patients, records from an ongoing longitudinal study of the neuropsychological manifestations of HIV infection were retrospectively reviewed. Of 252 participants (218 HIV-seropositive, 34 HIV-seronegative) who underwent at least one diagnostic lumbar puncture, 9 (7 seropositive, 2 seronegative) required EBP for post-dural puncture headache. After EBP, 6 of the seropositive subjects underwent serial neuropsychological evaluations over periods ranging from 6 to 24 months; none of these six subjects had a decline in neurocognitive performance or other adverse neurologic or infectious sequelae. We were unable to identify morbidity attributable to EBP in the HIV-seropositive patient followed for as long as 2 yr.

Adult

Relationship of cerebrospinal fluid immune activation associated factors to HIV encephalitis.

OBJECTIVES AND DESIGN: Because macrophages are the predominant immune cell and the predominant infected cell in the brains of patients with HIV encephalitis, we studied macrophage and immune activation-associated factors in the cerebrospinal fluid (CSF) from 39 autopsied AIDS cases for whom complete neuropathologic evaluation of the brain was available. RESULTS: CSF HIV p24 antigen was present in less than one-third of cases (11 out of 39). Less than half of the autopsies with moderate to severe parenchymal infection by HIV had high levels of CSF p24, although all autopsies with elevated levels of HIV p24 had moderate to severe HIV encephalitis. Elevated levels of cytokines, beta 2-microglobulin, neopterin, and quinolinic acid were observed. CONCLUSIONS: Although many of the CSF findings showed a strong correlation with each other, none showed a strong correlation with the severity of HIV infection of the brain itself. The absence of a close association between CSF abnormalities and HIV encephalitis could reflect the abundance of complicating opportunistic infections in these terminally ill patients or the inadequacy of CSF as a marker of basal ganglia involvement in HIV encephalitis. These findings complicate interpretation of clinical studies of CSF in patients with AIDS where neuropathologic evaluation is unavailable.

AIDS Dementia Complex

The relationship of life adversity, social support, and coping to hospitalization with major depression.

We evaluated the relationship between life events, social support, coping, and depression in 27 male inpatients meeting the requirements for Research Diagnostic Criteria major depressive disorder and in 35 age- and sex-matched nonpatients. Overall, the hospitalized depressed patients reported significantly more events and difficulties than did the controls, but this difference in statistical significance disappeared after excluding from analysis "non-independent" happenings which could have been brought on by depression. More hospitalized depressed patients (23 of 27, or 85%) than controls (8 of 35, or 22.9%) experienced markedly threatening events and difficulties ("marked adversities") in the 6 months before their interview. The depressed group also reported having significantly fewer social supports, being less satisfied with the emotional component of this support, and using more emotion-focused coping than the controls. A discriminant analysis predicted depressive status from a combination of marked adversities, reduced number of social supports, and greater use of emotion-focused coping. The results indicate that the relationship of life events to depression is complex. The excess number of events might be partly a product of dysfunctional behavior that "produces" depression-related events which might, in turn, exacerbate depression; simultaneously, patients are more likely to experience highly adverse events which might precipitate the depression in the first place. Reduced social supports and the use of emotion-focused coping appear to also be associated with hospitalization for major depression.

Adaptation, Psychological

Long-term abstinent alcoholics have normal memory.

It is generally believed that many non-Korsakoff alcoholics have subtle defects in memory. To determine whether such defects vary as a function of length of abstinence (LOA), we performed extensive memory testing with: (1) recently detoxified (n = 31; LOA-29 days); (2) intermediate-term abstinent (n = 28; LOA = 1.9 years); (3) long-term abstinent (n = 32; LOA-7.0 years) alcoholics; and (4) nonalcoholic controls (n = 37). All subjects were matched on age and education. Alcoholics were matched on years of alcoholic drinking. Memory measures were divided into the following domains: verbal learning, verbal recall, visual learning, visual recall, and paired associate learning. A series of MANOVAs were conducted that revealed a significant relationship between visual learning and length of abstinence, and a significant interaction between age and length of abstinence on visual recall. Long-term abstinent subjects were not significantly different from controls on any test. We conclude that memory disturbance demonstrable among recently detoxified alcoholics in the early weeks of their abstinence is not evident in demographically matched long-term abstinent alcoholics with similar drinking histories.

Adult

Incidence of AIDS dementia in a two-year follow-up of AIDS and ARC patients on an initial phase II AZT placebo-controlled study: San Diego cohort.

In a prospective study to determine the incidence of clinical dementia in patients with AIDS and ARC, 29 men and 3 women, 19 with ARC and 13 with AIDS, were examined neurologically and neuropsychologically every 6 months for 2 years during a placebo-controlled zidovudine (AZT) licensing trial. Most received two MRI brain scans. Although no patient was clinically demented at baseline, 9 (28%) developed dementia during the 2 years. Progression to dementia was associated with neuropsychological deterioration and with worsening on MRI during a preceding 6-month period, but not with baseline treatment group assignment. The results suggest that patients at CDC Stage IV who do not receive antiretroviral treatment earlier in their illness may develop clinical dementia at an annual rate of about 14%.

AIDS Dementia Complex